To be eligible for consideration this Application form must be sent by email to [email protected] latest on September 15th, 2025.
Please note that by submitting this Application and, if accepted for participation, by making one or more Submissions to this CACHE Challenge, you are agreeing on behalf of yourself and your organization to the CACHE Terms of Participation, found here:
Please fill in all fields in this form in order to be eligible to participate.
Applications will be pre-screened at CACHE to ensure that the Applicant research group or company has published in the field or otherwise has appropriate qualifications. Applications will then go through a double-blind peer-review process where the Computational Approach Description(s) submitted below will be available to the reviewers. Each Applicant that passes the pre-screen stage will be asked to review the quality of the Computational Approach from five other Applicants (without identifying Applicants) and to verify that the Computational Approach Descriptions are sufficiently detailed that an expert in the field could readily understand the Applicants’ prediction strategies. Applications that pass the double-blind peer-review stage will be reviewed by an independent committee convened by CACHE that will select up to 25 Applicants to participate and make submissions of binding predictions to this CACHE Challenge1. All selected Participants will be anonymized2.
1. CACHE has no obligation to accept any particular Application but, resources permitting, will strive to accept all Applications with viable Computational Approach Descriptions and appropriate Applicant qualifications, as determined by CACHE in its discretion.
2. Disclosing your publications may reveal your identity to visitors. They may use this information to determine from preliminary results disclosed at the end of Round #1 whether you advanced to Round #2, and how efficient your method was overall at the end of Round #2.
As noted above, please note that by submitting this Application and, if accepted for participation, by making one or more Submissions to this CACHE Challenge, you are agreeing on behalf of yourself and your organization to the CACHE Terms of Participation, found here.
CACHE will cover 100% of the costs of testing compounds experimentally. 100% of the costs of procuring compounds (either make-on-demand or custom-synthesized compounds) will be covered by participants. To lower the costs, CACHE will agree with Enamine on a preferred bulk price. CACHE will cover 50% of the costs for eligible Canadian academics and Canadian SMEs through a Strategic Innovation Fund awarded to Conscience by the Canadian government.
The information in this section will be maintained confidential unless you click otherwise below, or are in the top three performing Participant’s in this CACHE Challenge.
Details of the corresponding applicant (to whom emails will be sent):
If your application is accepted:
You will have two months starting October 15th 2025, with a Submission deadline of December 15th 2025, to specify 100 compounds identifying orthosteric inhibitors that are selective for PGK2 over its close homologue PGK1. Compounds should be commercially available at modest cost. We favor the Enamine Real Database (via ZINC) catalog, subsets of which may be downloaded from http://cache.docking.org/ or obtained directly from Enamine. Please provide SMILES and purchasing information for each compound (ZINC ID, Enamine ID, etc). CACHE will purchase your selected compounds (with the usual caveats about make-on-demand compounds), test them experimentally (see below) and send all data back to you, including the KD of active molecules measured by SPR by July 1st2026. To save costs, we ask that you purchase “flat” molecules, without stereochemical resolution, as they are generally cheaper. We will attempt to purchase the lowest cost form of the compound available, requesting a salt form for solubility if available, unless otherwise requested.
In addition to submitting their predictions by December 15th2025, Participants using de novo design approaches will be responsible for having their predicted compounds and associated analytical spectra showing >95% purity received at CACHE by January 15th 2026.
This section will be used for double-blind peer-review and will be disclosed on cache-challenge.org anonymously (except as described above) after all participants have submitted their first compound selection:
By August 1st, 2026 barring unforeseen circumstances, you will receive an SDF file with the 2D structure of all compounds selected by all Participants at the hit identification phase, but without any experimental data. You will be asked to predict actives among these compounds by October 1st 2026
This section will be used for double-blind peer-review and will be disclosed on cache-challenge.org anonymously (except as described above) after all merged selection participants have submitted their merged selection:
By July 1st 2026, barring unforeseen circumstances, you will have received all experimental data for the compounds that you selected that were successfully delivered to CACHE. From among the hits (KD < 100 µM) that emerge from your work, you will be asked to select by September 1st 2026 an additional 50 compounds from http://cache.docking.org/ to explore the structure-activity relationship of these experimental hits. Your file should contain the ZINC/Enamine catalog numbers and SMILES string of each compound. CACHE will purchase as many of your selected compounds as can be made economically by parallel synthesis at Enamine, test them experimentally, measure the solubility and purity of the highest affinity hits, and send all data back to you, including the KD of active molecules measured by SPR by February 1st 2027.
If this second selection is not from the Enamine Real Database, participants will be responsible for synthesis and for having the compounds and associated analytical spectra showing >95% purity received at CACHE by January 15th, 2026
This section will be used for double-blind peer-review and will be disclosed on cache-challenge.org anonymously (except as described above) after all hit-optimization participants have submitted their selection of optimized compounds
On June 1st 2027, barring unforeseen circumstances, CACHE will publicly release the anonymized list of participants and their origin (academia, biotech, pharma etc.). As described above, Participant identity will be de-anonymized if they are a top three performer or have consented to release of their identity above. Information about a Participant’s software and/or reproducible workflows will be released if the Participant has consented above. For all Participants the following will be released:
Methods will be evaluated and ranked using a traffic-light scoring scheme detailed in https://doi.org/10.33774/chemrxiv-2021-rzq4n
As noted above, please note that by submitting this Application and, if accepted for participation, by making one or more Submissions to this CACHE Challenge, you are agreeing on behalf of yourself and your organization to the CACHE Terms of Participation, found here: CACHE_Terms_of_Participation.
